The present invention relates to a substance having an apoptosis-inducing ability useful in the field of pharmaceutical agents, foods and beverages, a method for the manufacture thereof, and pharmaceutical agents, foods and beverages containing said substance having an apoptosis-inducing ability.
In recent years, a mode of apoptosis has been drawing the attention concerning the death of cell tissues. Unlike necrosis which is a pathological cell death, apoptosis is a death which is integrated from the first in gene of the cell itself. Thus, a programmed death gene protein is biosynthesized by activating gene which programs the apoptosis where some external or internal cause acts as a trigger, or in other case, a programmed death protein which exists within a cell as non-activated type is activated. It is believed that the cell itself is degraded by the produced programmed death protein of activated type whereby death of the cell is resulted. If such apoptosis can be expressed in desired tissues or cells, it will be now possible to exclude the unnecessary or harmful cells from living body in their natural form and that will be significantly meaningful.
An object of the present invention is to offer a substance having an apoptosis-inducing ability useful in the field of pharmaceutical agents, foods and beverages, to offer a method for the manufacture thereof, and furthermore to offer pharmaceutical agents, foods and beverages containing said substance having an apoptosis-inducing ability as an effective component:
The present inventors have carried out an intensive investigation for achieving the above-mentioned objects, found that a heat-treated product obtained by heating at least one compound selected from (a) pentose, (b) pentose derivatives such as deoxyribose, (c) compounds containing pentose such as ribonucleoside, ribonucleotide and ribonucleic acid, and (d) compounds containing pentose derivative such as deoxyribonucleoside, deoxyribonucleotide and deoxyribonucleic acid has a strong apoptosis-inducing action to cancer cells, succeeded in isolating a substance having an apoptosis-inducing ability which is an active component of said heat-treated product and accomplished the present invention.
Summary of the present invention is as follows. Thus, the first feature of the present invention relates to a method for the manufacture of a substance having an apoptosis-inducing ability characterized in including a step of subjecting at least one compound selected from the following (a), (b), (c) and (d) [excluding uronic acid and/or uronic acid derivatives; and compounds which contain uronic acid and/or uronic acid derivatives] to a heating treatment:
(a) pentose;
(b) pentose derivatives;
(c) compounds containing pentose;
(d) compounds containing pentose derivatives.
As an embodiment of the first feature of the present invention, ribose or xylose is exemplified as pentose although the present invention is not limited thereto. Examples of the pentose derivatives are deoxypentose such as deoxyribose and pentose derivatives where a group capable of having a negative charge such as phosphoric acid group or sulfuric acid group is bonded at 5-position. Examples of the compounds containing pentose are ribonucleoside, ribonucleotide, ribonucleic acid and pentose where a group of capable of having a negative charge such as phosphoric acid group or sulfuric acid group is bonded at 5-position. Examples of the compounds containing pentose derivatives are deoxyribonucleoside, deoxyribonucleotide and deoxyribonucleic acid. Examples of the substance having an apoptosis-inducing ability are the compounds selected from 4,5-dihydroxy-2-pentenal, 4-hydroxy-2-cyclopenten-1-one, 4-(9-adeninyl)-2-cyclopenten-1-one, 4-(9-guaninyl)-2-cyclopenten-1-one, 1,5-epoxy-1-hydroxy-3-penten-2-one and 4,5-dihydroxy-2-cyclopenten-1-one.
The second feature of the present invention relates to an apoptosis-inducing compound selected from 4-(9-adeninyl)-2-cyclopenten-1-one, 4-(9-guaninyl)-2-cyclopenten-1-one, 1,5-epoxy-1-hydroxy-3-penten-2-one, 2-(3,4-dihydroxy-1-butenyl)-4-(2-formylvinyl)-1,3-dioxolane and the compound represented by the following formula [I]. 
(In the formula, R is a residual group after removal of an SH group from a compound containing an SH group.)
Examples of the compound containing an SH group in the embodiment of the second feature of the present invention are cysteine and glutathione although the present invention is not limited thereto.
The third feature of the present invention relates to a pharmaceutical agent for therapy or prevention of a disease having a sensitivity to a compound selected from 4,5-dihydroxy-2-pentenal, 4-hydroxy-2-cyclopenten-1-one, 4-(9-adeninyl)-2-cyclopenten-1-one, 4-(9-guaninyl)-2-cyclopenten-1-one, 2-(3,4-dihydroxy-1-butenyl)-4-(2-formylvinyl)-1,3-dioxolane, 1,5-epoxy-1-hydroxy-3-penten-2-one and a compound represented by the formula [I], characterized in that, said pharmaceutical agent contains a compound selected from 4,5-dihydroxy-2-pentenal, 4-hydroxy-2-cyclopenten-1-one, 4-(9-adeninyl)-2-cyclopenten-1-one, 4-(9-guaninyl)-2-cyclopenten-1-one, 2-(3,4-dihydroxy-1-butenyl)-4-(2-formylvinyl)-1,3-dioxolane, 1,5-epoxy-1-hydroxy-3-penten-2-one and a compound represented by the formula [I] as an effective component.
Examples of the pharmaceutical agent in the embodiment of the third feature of the present invention are anticancer agent, apoptosis inducer, antirheumatic agent, inducer for production of human insulin-like growth factor, suppressor of the active oxygen production and inducer of the heat shock protein although the present invention is not limited thereto.
The fourth feature of the present invention relates to food or beverage where a substance having an apoptosis-inducing ability obtained by subjecting at least one compound selected from the following (a), (b), (c) and (d) [excluding uronic acid and/or uronic acid derivatives; and compounds which contain uronic acid and/or uronic acid derivatives] to a heating treatment and/or a partially purified product thereof are/is contained therein, diluted therewith and/or added thereto:
(a) pentose;
(b) pentose derivatives;
(c) compounds containing pentose;
(d) compounds containing pentose derivatives.
Examples of the food or beverage in the embodiment of the fourth feature of the present invention are carcinostatic, apoptosis-inducing, antirheumatic, human insulin-like growth factor production inducing, active oxygen production suppressing and heat shock protein inducing food or beverage although the present invention is not limited thereto.